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Journal of Neuroimmune Pharmacology

, Volume 7, Issue 1, pp 165–172 | Cite as

Nitric Oxide Decreases the Enzymatic Activity of Insulin Degrading Enzyme in APP/PS1 Mice

  • Markus P. Kummer
  • Claudia Hülsmann
  • Michael Hermes
  • Daisy Axt
  • Michael T. HenekaEmail author
ORIGINAL ARTICLE

Abstract

Nitric oxide has been implicated in the regulation of enzyme activity, particularly the activity of metalloproteinases. Since the inducible form of the nitric oxide synthase (NOS2), is upregulated in Alzheimer’s disease, we investigated the activity of two amyloid β degrading enzymes, IDE and neprilysin. In vitro we demonstrated that the activity of IDE was inhibited by *NO donor Sin-1, whereas activity of neprilysin remained unaffected. In vivo the activity of insulin-degrading enzyme was lowered in APP/PS1 mice, but not in APP/PS1/NOS2(−/−) mice. These data suggest that NOS2 upregulation impairs amyloid β degradation through negative regulation of IDE activity and thus loss of NOS2 activity will positively influence amyloid β clearance.

Keywords

IDE Insulin degrading enzyme Nitric oxide Aβ Nitration 

Abbreviations

AEBSF

4-(2-aminoethyl) benzenesulfonyl fluoride hydrochloride

PN

Peroxynitrate

Sin-1

3-morpholino-sydnonimine

DetaNONOate

(Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate

GSNO

S-Nitrosoglutathione

Notes

Conflict of interest

The authors declare no conflict of interest.

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Markus P. Kummer
    • 1
  • Claudia Hülsmann
    • 1
  • Michael Hermes
    • 1
  • Daisy Axt
    • 1
  • Michael T. Heneka
    • 1
    Email author
  1. 1.Clinical Neurosciences Unit, Department of NeurologyUniversity of BonnBonnGermany

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